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Aggrecan and collagen turnover in normal and degenerate human intervertebral discs using racemization of aspartic acid

We have used the racemization of aspartic acid as marker for "molecular age" of collagen and aggrecan component of the human intervertebral disc matrix i.e. aggregating and non-aggregating proteoglycan as well as different buoyant density fractions of the aggrecan. By measuring the D/LAsp ratio of the different aggrecan species as a function of age, and using the values of the racemization constant, ki, found earlier for aggrecan in articular cartilage, we were able to establish directly the relative residence time of these molecules in human intervertebral disc matrix.

For collagen, the half life value is around 125 years for both the nucleus pulposus and the annulus fibrosus. For the large monomer, the half life is 5.5 +/- 1.5 years - similar to the 3.4 years previously found on human articular cartilage, whereas for the binding region (A1D6), this value is 21.5 +/- 0.6 years - similar to 25 years in articular cartilage. For A1 preparations taken from normal tissue, half-life of 12.2.0 and 11.23.1.86 years were found for nucleus pulposus and annulus fibrosus, respectively; respective values from degenerate tissue are 8.77.2.17 and 8.41 +/- 2.83 years, suggesting increased synthesis of intact monomer (A1D1) in the degenerate tissue and/or increased rate of removal of small aggrecan fragments. A1-preparations from nucleus pulposus contain a lower proportion of aggregating proteoglycans compared to annulus fibrosus, suggesting increased proteolytic modification in the nucleus pulposus.

In view of the high half life values of both collagen and aggrecan (especially collagen), questions arise as to the real possibilities of regenerating and repairing tissue.

These finding are sent for publication (not confidential).

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Alice MAROUDAS, (Professor)
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